Alemtuzumab in Combination With Methylprednisolone Is a Highly Effective Induction Regimen for Patients With Chronic Lymphocytic Leukemia and Deletion of TP53: Final Results of the National Cancer Research Institute CLL206 Trial
Alemtuzumab in Combination With Methylprednisolone Is a Highly Effective Induction Regimen for Patients With Chronic Lymphocytic Leukemia and Deletion of TP53: Final Results of the National Cancer Research Institute CLL206 Trial
复制标题
DOI：
10.1200/jco.2011.35.9695
复制
发表时间：
2012-05-10
影响因子：
45.3
通讯作者：
Hillmen, Peter
中科院分区：
文献类型：
--
作者：
Pettitt, Andrew R.;Jackson, Richard;Hillmen, Peter
在慢性淋巴细胞白血病（CLL）中，TP 53缺失/突变与不良结局和对化疗耐药密切相关。相反，TP 53缺陷与抗CD 52单克隆抗体阿仑单抗或甲泼尼龙的耐药性无关。为了改善TP 53缺陷型CLL的治疗，开展了一项多中心II期研究，以评估阿仑单抗和甲基强的松龙的联合治疗。（17例未治疗和22例既往治疗）接受长达16周的Alemtuzumab 30 mg每周3次和甲基强的松龙1.0 g/m治疗（2）每4周连续5天。抗菌预防包括复方新诺明、伊曲康唑和阿昔洛韦（或缬更昔洛韦用于无症状巨细胞病毒血症）。主要终点是终点审查委员会指定的反应。次要终点为安全性、无进展生存期（PFS）和总生存期（OS）。（包括骨髓恢复不完全），中位PFS和中位OS在整个队列中分别为85%、36%、11.8个月和23.5个月，在整个队列中分别为88%、65%、18.3个月和38.9个月，在以前未经治疗的患者中。分别有67%和23%的患者发生3 - 4级血液学和糖皮质激素相关毒性。总体队列中51%的患者和29%的60岁以下患者发生3 - 4级感染。结论阿仑单抗联合甲泼尼龙是目前报道的TP 53缺失型CLL最有效的诱导治疗方案。感染风险与年龄有关，在年轻患者中，似乎仅略高于利妥昔单抗、氟达拉滨和环磷酰胺。
PurposeIn chronic lymphocytic leukemia (CLL), TP53 deletion/mutation is strongly associated with an adverse outcome and resistance to chemotherapy-based treatment. In contrast, TP53 defects are not associated with resistance to the anti-CD52 monoclonal antibody alemtuzumab or methylprednisolone. In an attempt to improve the treatment of TP53-defective CLL, a multicenter phase II study was developed to evaluate alemtuzumab and methylprednisolone in combination.Patients and MethodsThirty-nine patients with TP53-deleted CLL (17 untreated and 22 previously treated) received up to 16 weeks of treatment with alemtuzumab 30 mg three times a week and methylprednisolone 1.0 g/m(2) for five consecutive days every 4 weeks. Antimicrobial prophylaxis consisted of cotrimoxazole, itraconazole, and aciclovir (or valganciclovir for asymptomatic cytomegalovirus viremia). The primary end point was response as assigned by an end-point review committee. Secondary end points were safety, progression-free survival (PFS) and overall survival (OS).ResultsThe overall response rate, complete response rate (including with incomplete marrow recovery), median PFS, and median OS were 85%, 36%, 11.8 months, and 23.5 months, respectively, in the entire cohort and 88%, 65%, 18.3 months, and 38.9 months, respectively, in previously untreated patients. Grade 3 to 4 hematologic and glucocorticoid-associated toxicity occurred in 67% and 23% of patients, respectively. Grade 3 to 4 infection occurred in 51% of the overall cohort and in 29% of patients less than 60 years of age. Treatment-related mortality was 5%.ConclusionAlemtuzumab plus methypredisolone is the most effective induction regimen hitherto reported in TP53-deleted CLL. The risk of infection is age related and, in younger patients, seems only marginally higher than that associated with rituximab, fludarabine, and cyclophosphamide.